Rejected

/Objective: Although SARS-CoV2 vaccines have been developed with multiple novel technologies and rapidly disseminated worldwide, the full profile of adverse effects has not been known. Recently, there are sporadic but increasing reports of endocrinopathy in relation to SARS-CoV2 vaccination. Here we report a rare case of hypophysitis with acute onset of diabetes insipidus, immediately after SARS-CoV2 vaccination.

The COVID-19 pandemic and the lockdown measures are both causes of psychological distress. The aim of the current study was to evaluate the psychological effects of lockdown measures on patients with subjective chronic tinnitus diagnosed before the COVID-19 pandemic. A sample of = 77 patients with chronic tinnitus was contacted by mail/phone for a survey between June 2021 and September 2021. All patients filled out questionnaires on tinnitus distress (Tinnitus Handicap Inventory, THI), anxiety (Beck Anxiety Inventory, BAI) and depression (Beck Depression Inventory, BDI) and eight items of the Tinnitus Sample Case History (TSCH) about tinnitus history (i.e., loudness, pitch, perception, tinnitus location), stress, and related conditions (noise annoyance, vertigo/dizziness, headache). Forty patients with chronic tinnitus filled out the survey. No significant differences of total THI mean scores ( > 0.05) were found compared to the results obtained before the COVID-19 pandemic and after lockdown. Regarding depression and anxiety, the female population showed a significant increase in scores obtained from the BDI ( < 0.0170) and the BAI ( < 0.049). Only two patients (0.5%) were infected by COVID-19 (positive RT-PCR), and they did not report any worsening of tinnitus. According to the data of the literature, our patients experienced a heterogeneous course of tinnitus, and the severity of tinnitus was not significantly affected by lifestyle changes during the COVID-19 pandemic and lockdown.

Systemic inflammation can be triggered by infection, surgery, trauma or burns. During systemic inflammation, an overshooting immune response induces tissue damage resulting in organ dysfunction and mortality. Endothelial cells make up the inner lining of all blood vessels and are critically involved in maintaining organ integrity by regulating tissue perfusion. Permeability of the endothelial monolayer is strictly controlled and highly organ-specific, forming continuous, fenestrated and discontinuous capillaries that orchestrate the extravasation of fluids, proteins and solutes to maintain organ homeostasis. In the physiological state, the endothelial barrier is maintained by the glycocalyx, extracellular matrix and intercellular junctions including adherens and tight junctions. As endothelial cells are constantly sensing and responding to the extracellular environment, their activation by inflammatory stimuli promotes a loss of endothelial barrier function, which has been identified as a hallmark of systemic inflammation, leading to tissue edema formation and hypotension and thus, is a key contributor to lethal outcomes. In this review, we provide a comprehensive summary of the major players, such as the angiopoietin-Tie2 signaling axis, adrenomedullin and vascular endothelial (VE-) cadherin, that substantially contribute to the regulation and dysregulation of endothelial permeability during systemic inflammation and elucidate treatment strategies targeting the preservation of vascular integrity.

Neuropathic pain is often closely associated with nerve injury or inflammation, and the role of traditional nonsteroidal anti-inflammatory drugs as adjuvants for treating chemotherapy-induced peripheral neuropathic pain remains unclear. In this study, the potential synergistic antinociceptive effects of indomethacin-pregabalin and meloxicam-pregabalin were evaluated in paclitaxel-induced neuropathic pain and carrageenan-induced inflammatory pain in rodents. Although indomethacin and meloxicam alone only slightly relieved mechanical allodynia in the above two models, isobolographic analysis showed that the combination of indomethacin or meloxicam with pregabalin produced significant synergistic antinociceptive effects for paclitaxel-induced neuropathic pain (IN-PGB, experimental ED = [4.41 (3.13-5.82)] mg/kg, theoretical ED = [8.50 (6.62-10.32)] mg/kg; MEL-PGB, experimental ED = [3.96 (2.62-5.46)] mg/kg, theoretical ED = [7.52 (5.73-9.39)] mg/kg). In addition, MEL-PGB dosed via intraplantar injection into the left paw, intragastric injection, or intraperitoneal injection reversed paclitaxel-induced allodynia, indicating that they may act at multiple sites in the neuroaxis and periphery. However, indomethacin-pregabalin and meloxicam-pregabalin exerted antagonistic antiallodynic interactions in carrageenan-induced inflammatory pain in rats. Taken together, coadministration of indomethacin or meloxicam with pregabalin may possess potential therapeutic advantages for treating chemotherapy-induced neuropathic pain.

Fructose intolerance (FI) is a widespread non-genetic condition in which the incomplete absorption of fructose leads to gastro-intestinal disorders. The crucial role of microbial dysbiosis on the onset of these intolerance symptoms together with their persistence under free fructose diets are driving the scientific community towards the use of probiotics as a novel therapeutic approach. In this study, we evaluated the prevalence of FI in a cohort composed of Romanian adults with Functional Grastrointestinal Disorders (FGIDs) and the effectiveness of treatment based on the probiotic formulation EQBIOTA ( CECT 7484 and 7485 and CECT 7483). We evaluated the impact of a 30-day treatment both on FI subjects and healthy volunteers. The gastrointestinal symptoms and fecal volatile metabolome were evaluated. A statistically significant improvement of symptoms (i.e., bloating, and abdominal pain) was reported in FI patient after treatment. On the other hand, at the baseline, the content of volatile metabolites was heterogeneously distributed between the two study arms, whereas the treatment led differences to decrease. From our analysis, how some metabolomics compounds were correlated with the improvement and worsening of clinical symptoms clearly emerged. Preliminary observations suggested how the improvement of gastrointestinal symptoms could be induced by the increase of anti-inflammatory and protective substrates. A deeper investigation in a larger patient cohort subjected to a prolonged treatment would allow a more comprehensive evaluation of the probiotic treatment effects.

Utilizing pharmacogenomics (PGx) and integrating drug-induced phenoconversion to guide opioid therapies could improve the treatment response and decrease the occurrence of adverse drug events. Genetics contribute to the interindividual differences in opioid response. The purpose of this case report highlights the impact of a PGx-informed medication safety review, assisted by a clinical decision support system, in mitigating the drug-gene and drug-drug-gene interactions (DGI and DDGI, respectively) that increase the risk of an inadequate drug response and adverse drug events (ADEs). This case describes a 69-year-old female who was referred for PGx testing for uncontrolled chronic pain caused by osteoarthritis and neuropathy. The clinical pharmacist reviewed the PGx test results and medication regimen and identified several (DGIs and DDGIs, respectively) at Cytochrome P450 (CYP) 2C19 and CYP2D6. The recommendations were to: (1) switch tramadol to buprenorphine transdermal patch, an opioid with lower potential for ADEs, to mitigate a CYP2D6 DDGI; (2) gradually discontinue amitriptyline to alleviate the risk of anticholinergic side effects, ADEs, and multiple DDGIs; and (3) optimize the pregabalin. The provider and the patient agreed to implement these recommendations. Upon follow-up one month later, the patient reported an improved quality of life and pain control. Following the amitriptyline taper, the patient experienced tremors in the upper and lower extremities. When the perpetrator drug, omeprazole, was stopped, the metabolic capacity was no longer impeded; the patient experienced possible amitriptyline withdrawal symptoms due to the rapid withdrawal of amitriptyline, which was reinitiated and tapered off more slowly. This case report demonstrates a successful PGx-informed medication safety review that considered drug-induced phenoconversion and mitigated the risks of pharmacotherapy failure, ADEs, and opioid misuse.

Crohn's Disease (CD) refers to a chronic transmural bowel inflammation affecting a range between 5 and 15 per 100,000 person-years worldwide 1. In patients with stricturing CD, the transmural pattern of inflammation may trigger the development of sinus tracts able to connect to other tissues, leading to the formation of fistulas or abscesses 2. Intra-psoas abscesses are rare, affecting between 0.4-4.3% of patients with CD 3. We present the case of a 36-year-old male with no past medical history except for a two-week worsening lumbosciatalgia not responding to standard nonsteroidal anti-inflammatory drugs, who complained sudden abdominal pain, with right lower abdominal stiffness combined to a severe edema and erythema of the right lower limb, extended from the gluteus down to the knee, involving the anteromedial and posteromedial areas of his thigh. Patient was septic and CT scans revealed a large complex air-fluid collection within the right iliac region, involving terminal ileum, right retroperitoneum and right lateral abdominal wall towards the inner edge of his thigh. Diagnosis of CD was made on histopathology and the patient gained full recovery thanks to a prompt surgical intervention followed by high-dose antibiotic infusion and vacuum-assisted wound closure. Intra-psoas abscesses, albeit rare, are a known manifestation of CD and frequently lead to misdiagnosis because of their rarity and their unusual location easily mimicking other diseases. Therefore, clinician's awareness must be heightened for complicated CD in the setting of intra-psoas abscesses in order to avoid delayed treatment. KEY WORDS: Crohn disease, Psoas abscess, Sciatica, Late onset disorders, Negative pressure Wound therapy.

Inflammation or injury to the somatosensory nervous system may result in chronic pain conditions, which affect millions of people and often cause major health problems. Emerging lines of evidence indicate that reactive oxygen species (ROS), such as superoxide anion or hydrogen peroxide, are produced in the nociceptive system during chronic inflammatory and neuropathic pain and act as specific signaling molecules in pain processing. Among potential ROS sources in the somatosensory system are NADPH oxidases, a group of electron-transporting transmembrane enzymes whose sole function seems to be the generation of ROS. Interestingly, the expression and relevant function of the Nox family members Nox1, Nox2, and Nox4 in various cells of the nociceptive system have been demonstrated. Studies using knockout mice or specific knockdown of these isoforms indicate that Nox1, Nox2, and Nox4 specifically contribute to distinct signaling pathways in chronic inflammatory and/or neuropathic pain states. As selective Nox inhibitors are currently being developed and investigated in various physiological and pathophysiological settings, targeting Nox1, Nox2, and/or Nox4 could be a novel strategy for the treatment of chronic pain. Here, we summarize the distinct roles of Nox1, Nox2, and Nox4 in inflammatory and neuropathic processing and discuss the effectiveness of currently available Nox inhibitors in the treatment of chronic pain conditions.

Interscalene block is applied to control acute postoperative pain after arthroscopic rotator cuff repair (ARCR), typically with single-shot interscalene block (SSIB) or continuous interscalene indwelling catheter analgesia (IICA), and dexamethasone (Dex) for extending the analgesic effect. This study investigated whether perineural Dex can extend the postoperative analgesic effect of SSIB to match that of IICA. A total of 130 patients were recruited and divided into two groups (Group D, SSIB with perineural Dex, = 94; Group C, IICA, = 36). The surgical and anesthetic processes were identical except for the method of nerve block. Pain was measured by a visual analog scale (VAS) at 6, 12, 24, and 48 h after ARCR. The number of each and the total analgesics used and adverse effects were compared. The duration of ARCR was longer in group D. The VAS score was higher in group C 6 h after ARCR, but there was no difference at other time points. More postoperative analgesics were administered to group C, and there was no difference in the number of adverse effects. In conclusion, combining perineural Dex with SSIB can reduce rebound hyperalgesia after 6 h and extend the duration of the analgesic effect to that of IICA. Therefore, IICA could be substituted with SSIB and Dex between at 6 and 48 h after ARCR.

The innate immune system is the first line of defense against invading pathogens or sterile injuries. Pattern recognition receptors (PRR) sense molecules released from inflamed or damaged cells, or foreign molecules resulting from invading pathogens. PRRs can in turn induce inflammatory responses, comprising the generation of cytokines or chemokines, which further induce immune cell recruitment. Neutrophils represent an essential factor in the early immune response and fulfill numerous tasks to fight infection or heal injuries. The release of neutrophil extracellular traps (NETs) is part of it and was originally attributed to the capture and elimination of pathogens. In the last decade studies revealed a detrimental role of NETs during several diseases, often correlated with an exaggerated immune response. Overwhelming inflammation in single organs can induce remote organ damage, thereby further perpetuating release of inflammatory molecules. Here, we review recent findings regarding damage-associated molecular patterns (DAMPs) which are able to induce NET formation, as well as NET components known to act as DAMPs, generating a putative fatal circle of inflammation contributing to organ damage and sequentially occurring remote organ injury.